Project Summary/Abstract This Mentored Patient-Oriented Research Career Development Award will provide S. Christy Sadreameli, M.D., M.H.S. with experience and training to become an independent investigator in pediatric pulmonology with a focus on the effects of environmental exposures on pulmonary morbidity and inflammation in sickle cell anemia (SCA). Despite advances in the prevention and treatment of SCA, affected children and young adults continue to suffer from a substantial amount of pulmonary morbidity, including episodes of acute chest syndrome (ACS) and respiratory symptoms such as cough and wheezing. Few modifiable risk factors have been identified in SCA, but emerging data suggest that exposure to SHS and other environmental factors are associated with pulmonary morbidity. Indoor environmental exposures such as secondhand smoke (SHS) and sensitization/exposure to mouse and cockroach are potential sources of pulmonary inflammation and morbidity in SCA. This proposal focuses on these common exposures that are likely to occur in the homes of children with SCA, many of whom live in cities and are impacted by poverty. This proposal will extend Dr. Sadreameli?s previous line of research that demonstrated a strong association between a biomarker of tobacco exposure (salivary cotinine) and SCA morbidity. This project will link objective measurement of SHS, mouse, and cockroach exposure with clinical pulmonary outcomes and several non-invasive measures of neutrophilic and eosinophilic lower airway inflammation to provide novel data about the impact indoor environmental exposures have on pulmonary morbidity and inflammation in SCA. Aim 1 will evaluate associations between SHS, pulmonary outcomes, and neutrophilic inflammation. Aim 2 will evaluate associations between allergic sensitization and exposure to mouse and cockroach, pulmonary outcomes, and eosinophilic inflammation. With this proposal, Dr. Sadreameli will build upon her previous experience and training to gain valuable expertise in environmental exposure assessment and non-invasive measurement of lower airway inflammation. This research project is likely to lead to future clinical trials of environmental modification of home-based interventions. Further, it will provide meaningful data about the inflammatory mechanisms of lower airway disease in SCA. Dr. Sadreameli has assembled a multidisciplinary research team with extensive research and mentorship experience. Her primary mentor, Sharon McGrath- Morrow, M.D., is a pediatric pulmonologist who will provide scientific mentorship with focus on measurement of pulmonary inflammatory and physiologic outcomes and career mentorship. Her co-mentors include James F. Casella, M.D., a pediatric hematologist who will provide training and expertise related to sickle cell disease pathophysiology and biomarkers of systemic inflammatory outcomes, Michelle Eakin, Ph.D., a behavioral psychologist who will provide training in behavioral modification and expertise related to the study of social determinants of health, and Kirsten Koehler, Ph.D., an environmental health scientist who will provide mentorship related to the measurement of and health effects from environmental exposures. The research and career development program and the guidance and expertise of her mentors will help Dr. Sadreameli succeed in her long-term goal of becoming a successful independent investigator.